Six structurally diverse alkaloids, named atrorosins A-F ( 1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus. These compounds represent the first reported natural products featuring an unprecedented hybrid architecture comprising a heptanone-substituted isoquinoline core conjugated with a butenoic acid-derived lactone moiety. Their structures were elucidated by 1D and 2D NMR spectra, and the absolute configuration of 1-6 was established by electronic circular dichroism (ECD) analyses. Compound 4, 6 demonstrated antibacterial activities with MIC = 1.46 μg/mL and 5.86 μg/mL, respectively. All compounds exhibited a potential antioxidant effect. The anti-inflammatory activity of compound 2, 5 was stronger than dexamethasone. Moreover, compound 2, 5 showed a good inhibitory effect on MTT proliferation in MCF breast cancer and SW480 colorectal cancer cells. This study not only expands the chemical diversity of fungal alkaloids but also provides lead compounds for multidrug-resistant pathogen and oncology therapeutics.